Mental retardation (MR) is believed to occur with a prevalence of ˜2% within the population. MR is significantly more frequent in males than in females, and for that reason it had been assumed that ˜25% of severe cases were X-linked, however recent review of data suggests that X-linked mutations contribute to no more than 10% of cases (Ropers & Hamel, 2005). Very little, however, is currently known about autosomal non-syndromic forms of MR. Autosomal dominant MR tends to occur only sporadically, due to the decreased likelihood of patients to procreate. Autosomal recessive forms of non-syndromic MR (NS-ARMR) are believed to be more common, yet only 5 genes have been identified so far, including PRSS12 (MRT1 on 4q25-q26; Molinari et al, 2002), CRBN (MRT2A on 3p26.2; Higgins et al, 2004), and CC2D1A (MRT3 on 19q13.12; Basel-Vanagaite et al, 2006). A recent study, using homozygosity mapping in large consanguineous families from Iran, has identified a further 8 loci (MRT4-12; Najmabadi et al, 2007). From this study, the discovery of GRIK2 as the cause of MRT6 on 6q21 (Motzacker et al, 2007), and TUSC3 on 8q12 as the cause of MRT7 have recently been made (Garshasbi et al, 2008).
The contribution of genetic factors to autism is also well established, but the mode of genetic transmission is unclear. It is apparent, however, that autism is a complex non-Mendelian disorder, and it is anticipated that genetic heterogeneity and oligo/polygenic inheritance are involved. Several genome-wide linkage studies have been performed, implicating a number of chromosomes, including 7q, 16p, 19q and 11p (IMGSAC, 1998 & 2001; CLSA, 1999; Liu et al, 2001; AGP 2007), however no genes have been identified so far. Evidence from studies of overlap between autism and mental retardation syndromes, as well as a number of studies using cytogenetic aberrations, also genomic copy number variants inferred from microarray analysis, have now implicated a number of specific genes such as SHANK3, NLGN3 & 4, NRXN1, CNTNAP2, UBE3A, FMR1, MECP2 and others (see reviews by Abrahams & Geschwind, 2008; Sutcliffe 2008). However, only very recently, several groups have started exploring the hypothesis that at least a small proportion of autism may be inherited in an autosomal recessive mode. The recent paper by Morrow et al (2008), where several genes such as PCDH10 and DIA1 were mapped through the identification of large homozygous deletions in consanguineous families with autism from the Arabian peninsula, Turkey and Pakistan, is an example of some of the potential of such an approach. Identification of autosomal recessive genes for autism may lead to the identification of relevant etiological biological pathways, and potentially the identification of other genes from the same pathway that may contribute to autism, and possibly inherited in a non-Mendelian fashion.
There is a need in the art to identify genetic markers associated with mental retardation and autism. Further there is a need in the art to identify nucleotide sequences associated with mental retardation and autism. There is also a need in the art for new diagnostic assays for mental retardation and autism.